title: A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses.
abstract: Clinicopathological, immunohistochemical and molecular genetic analyses of endometrial carcinoma suggest different pathogenetic pathways for endometrioid and serous carcinoma. Most endometrioid carcinomas are associated with endometrial hyperplasia, are ER/PR positive, p53 negative and express low Ki-67. In contrast, almost all serous carcinomas develop from endometrial intraepithelial carcinoma (EIC) in a background of atrophy. These tumors are ER/PR negative, strongly express p53 and show high Ki-67 labeling. On the molecular genetic level, 25-30% of endometrioid carcinomas show microsatellite instability (MI), 25-30% harbor mutant K-ras and less than 10% have mutant p53. In contrast, more than 90% of serous carcinomas have p53 mutations, 2% K-ras mutations and none MI. Among endometrioid carcinomas, K-ras mutations occur most frequently in FIGO grade 2 and 3 tumors and p53 mutations in FIGO grade 3 tumors. In contrast, MI is equally distributed among all FIGO grades. These findings support the view that endometrioid carcinoma develops slowly in a progressive fashion from endometrial hyperplasia. Mutation of p53 occurs late in tumor progression. Thus, endometrioid carcinogenesis resembles the proposed model for colorectal carcinogenesis. In contrast, serous carcinoma develops rapidly from EIC in a background of atrophy. Mutation of p53 occurs early in serous carcinogenesis and this may account for the highly aggressive behavior of this tumor.
authors.affiliation: Department of Pathology, John Hopkins Medical Institutions, Baltimore, Md. 21287, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Lax
authors.forename: R J
authors.initials: RJ
authors.lastname: Kurman
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53